Tosyl displacement with alkoxide

Other Alkyl and Aryl Ethers - A number of 3-0-aminoalkyl-l,2-0-isopro-pylidene-a-D-gluco-or xylo-furanoses have been synthesized and evaluated for antiviral activity. Some 6-0-alkyl-a-D-glycopyranosides have been prepared by displacement of 6-0-tosylates with alkoxides, while the regioselectivity of 3- or 5-0-ether formation on l,2-0-isopropylidene-4,6-di-0-benzyl-/n> o-inositol has been shown to depend on the nature of the 0-alkylating agent. A facile synthesis of methyl 2-or 3-0-allyl-5-0-benzyl-p-D-ribofuranoside has been described. ... 

Tosylate is displaced by weak oxyanions with little elimination in aprotic solvents, providing alternative routes to polymer-bound esters and aryl ethers. Alkoxides, unfortunately, give significant functional yields of (vinyl)polystyrene under the same conditions. Phosphines and sulfides can also be prepared from the appropriate anions (57), the latter lipophilic enough for phase-transfer catalysis free from poisonning by released tosylate. 

A detailed study of the formation of n-octyl ethers under solidrliquid two-phase conditions in the absence of an added solvent has been reported [10], Potassium alkoxides tend to produce higher yields of the ethers than do the corresponding sodium derivatives, but octene is the major product in the reaction of 1-bromooctane with potassium t-butoxide. High temperatures also tend to promote the preferential formation of octene and slightly higher yields of the ethers are obtained using n-octyl tosylate in preference to n-octyl bromide. p-Fluorinated acetals have been prepared either under basic catalytic liquidrliquid or solidrliquid conditions from the fluori-nated alcohol and dichloromethane [11] with displacement of the fluorine atoms. 

Kinetic template effects have been involved in the formation of crown ethers, with respect to the cyclization step involving a nucleophilic displacement of halide or tosylate by alkoxide ions. It has been proposed that cyclization of the linear bifunctional precursor is enhanced by a cyclic conformation in which the alkoxide cation brings the two ends of the molecule into close proximity... 

The alkoxide ion is a strong nucleophile as well as a powerful base. Unlike the alcohol itself, the alkoxide ion reacts with primary alkyl halides and tosylates to form ethers. This general reaction, called the Williamson ether synthesis, is an SN2 displacement. The alkyl halide (or tosylate) must be primary so that a back-side attack is not hindered. When the alkyl halide is not primary, elimination usually results. 

Mechanistically, the Williamson synthesis is simply an 8 2 displacement of halide ion by an alkoxide ion nucleophile. The Williamson synthe sis is thus subject to all the usual constraints on 8 2 reactions discusser in Section 11.5. Primary halides and tosylates work best because competi tive E2 elimination of HX can occur with more hindered substrates. Unsym-metrical ethers should therefore be synthesized by reaction between thi more hindered alkoxide partner and less hindered halide partner rathe than vice versa. For example, tert-butyl methyl ether, a substance used c an octane booster in gasoline, is best prepared by reaction of ferf-butoxidc ion with iodomethane rather than by reaction of methoxide ion with 2-chloro-2-methylpropane. 

The yV-alkyl-substituted azadiol was treated with an equimolar amount of tosyl chloride and excess alkali metal hydroxide in an aprotic solvent (powdered NaOH, dioxane, room temperature, 3 hr) to give a 60% yield of the monoaza-crown (Kuo et al., 1978). Template effects are important in this cyclization reaction, so sodium hydroxide was used for aza-15-crown-5 and potassium hydroxide for aza-18-crown-6. The intramolecular ring-closure process is the result of the initial formation of a tosylate by the reaction of one alkoxide anion with tosyl chloride followed by displacement of the tosylate leaving group by the second alkoxide anion. The pure monoaza-crowns were isolated from their metal ion complexes by thermolysis under reduced pressure (Kuo et al., 1980). 

An example is 31, which reacts with the soft thiophenoxide (PhS) at the tosylate center (C-OTs) to give 32.5 Reaction of 31 with the harder cyanide ion, however, gives 33 and subsequent ring closure where the alkoxide unit displaces tosylate generates oxetane 34. Thiophenoxide is a soft base that reacts with the soft... 

In the synthesis of aspyrone (994), an antibiotic isolated from the culture broth of Aspergillus species, lactaldehyde 990 supplies the asymmetric centers of the epoxide in the side chain (Scheme 134). The molecule is assembled convergently by addition of the lithium enolate of D-rhamnose-derived a-phenylseleno- -lactone 991 to aldehyde 990. After an initial aldol-type reaction, the intermediate alkoxide displaces tosylate to provide epoxide 992 with >99.8% stereoselectivity. Peroxide-induced elimination of phenylselenide furnishes TBS-protected aspyrone 993 in 61% overall yield from 990. 

Silicon-Induced Domino Reactions. In a series of papers, Schaumann et al. disclosed the synthesis of various cyclic compounds utilizing a silicon-induced reaction cascade. Treatment of an epoxyalkyl tosylate with 2-lithio-2-TMS-l,3-dithiane leads to the corresponding lithium alkoxide. Subsequent 1,4-Brook rearrangement and displacement of the tosylates affords cyclopen-tanols in good yield (eq 24). ... 

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